FDA clears post-surgery drug duo for higher-risk clear cell kidney cancer

The U.S. Food and Drug Administration has approved a two-drug regimen for adults with higher-risk clear cell kidney cancer after surgery. The decision gives some patients with renal cell carcinoma with a clear cell component a new adjuvant treatment aimed at lowering the chance that the disease returns, according to Dana-Farber Cancer Institute.

The regimen combines pembrolizumab, an immunotherapy, with belzutifan, a HIF-2α inhibitor. The FDA approval covers adults with clear cell renal cell carcinoma at intermediate-high or high risk of recurrence after nephrectomy, with or without removal of metastatic lesions, Dana-Farber said.

The approval rests on results from the Phase III LITESPARK-022 trial, which was led by Toni Choueiri, director of the Lank Center for Genitourinary Oncology at Dana-Farber. Choueiri said the decision makes the pembrolizumab-belzutifan regimen a new adjuvant option for patients whose clear cell renal cell carcinoma carries an increased risk of coming back after surgery.

Trial showed fewer recurrences

LITESPARK-022 enrolled 1,841 people with clear cell renal cell carcinoma, according to Dana-Farber. Participants had undergone surgery to remove their tumor, had no detectable signs of cancer afterward and were considered at elevated risk for recurrence.

Researchers randomly assigned patients to receive either pembrolizumab plus belzutifan after surgery or pembrolizumab plus placebo. With a median follow-up of 28.4 months, Dana-Farber said the two-drug regimen reduced the risk of recurrence, metastasis or death by 28% compared with pembrolizumab plus placebo.

At an estimated 24 months, about 81% of patients who received pembrolizumab and belzutifan were cancer-free, compared with 74% of patients in the pembrolizumab-plus-placebo group, according to the trial results reported by Dana-Farber. The institute said side effects matched what had been seen in earlier studies.

Choueiri presented the trial findings at the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium, Dana-Farber said. The FDA also approved a subcutaneous combination of pembrolizumab and berahyaluronidase alfa-pmph with belzutifan.

First earlier-stage approval for belzutifan

Dana-Farber said the decision marks the first approval of belzutifan for earlier-stage clear cell renal cell carcinoma. It also marks the first approval of a regimen pairing a PD-1 inhibitor with a HIF-2α inhibitor, according to the institute.

Belzutifan is designed to block HIF-2α, a target that Dana-Farber said is overabundant in clear cell renal cell carcinoma cells and helps drive tumor growth. The institute also noted that William G. Kaelin Jr. of Dana-Farber received the 2019 Nobel Prize in Physiology or Medicine for science that contributed to belzutifan’s development.

Renal cell carcinoma is the most common form of kidney cancer, accounting for about nine in 10 kidney cancer diagnoses, according to Dana-Farber. Clear cell renal cell carcinoma makes up 75% of renal cell carcinoma diagnoses, the institute said.

Worldwide, about 435,000 new kidney cancer cases were diagnosed in 2022 and about 156,000 people died from the disease, according to figures cited by Dana-Farber. About 30% of patients with clear cell renal cell carcinoma have a recurrence within five years after nephrectomy, the institute said.

This story draws on original reporting from Medical Xpress.